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Biomedical subjects

S Yusuf

Publications and source records attributed to S Yusuf.

At least 217 records · Page 12Linked to original sources
PubMed1990

Expanding indications for the use of thrombolytic agents in acute myocardial infarction.

A large body of data from randomized clinical trials have definitely established that thrombolytic therapy in acute myocardial infarction reduces the risk of early mortality by approximately one fourth. Unfortunately, most (but not all) trials have been unduly restrictive in selecting patients who have been entered. Consequently, at least half of the patients (many of whom are at high risk of death) who present with signs and symptoms of acute myocardial infarction are not considered for such therapy. A critical analysis of the data from all the available trials indicates that thrombolytic therapy reduces mortality in a much broader group of patients than generally believed. For example, patients who present late (i.e., 6-24 h) after the onset of symptoms, those over the age of 75 years, those with classical symptoms but minor or no abnormalities on the first electrocardiogram, those with low or high blood pressure, and patients in several other subgroups have been shown to benefit. The absolute and relative risk of major adverse effects (such as major bleeding episodes or strokes) have been so low that in each of these subgroups the benefits of treatment far outweigh their potential risks.

Acute Disease↗
PubMed1990

Prognostic value of prolonged ventricular repolarization following myocardial infarction: the BHAT experience. The BHAT Study Group.

In the Beta Blocker Heart Attack Trial (BHAT), 3837 patients were randomized to propranolol (180-240 mg/day) or placebo 5-21 days after a documented myocardial infarction and were followed in a double blind manner for a mean period of 25 months. Twelve lead electrocardiograms were routinely obtained at the time of randomization (baseline electrocardiogram) and at 12 and 24 months of follow-up. There was a positive correlation between baseline QTc interval prolongation (but not QT prolongation) and mortality and sudden death that was independent of treatment group. The data for non-sudden death and non-fatal reinfarction exhibit similar trends. We conclude that: (1) QTc prolongation identifies a high risk subset of post myocardial infarction patients. (2) The relative benefit of propranolol is similar in patients with normal and prolonged QTc.

Death, Sudden↗
PubMed1990

Effects of tissue-type plasminogen activator and anisoylated plasminogen streptokinase activator complex on mortality in acute myocardial infarction.

An overview of eight randomized controlled trials of tissue-type plasminogen activator (Alteplase or Duteplase) and 10 of anisoylated plasminogen streptokinase activator complex (Anistreplase) showed that the odds of early death were reduced by 29% by tissue-type plasminogen activator and 46% by anisoylated plasminogen streptokinase activator complex, with overlapping 95% confidence intervals. Although the beneficial effects of both agents are consistent and are strengthened when all the trials are considered together, the available data do not permit comparisons of the relative efficacy of these two agents with each other or with streptokinase.

Anistreplase↗
PubMed1990

Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD).

Neuroendocrine activation is known to occur in patients with congestive heart failure, but there is uncertainty as to whether this occurs before or after the presence of overt symptoms. In the Studies of Left Ventricular Dysfunction (SOLVD), a multicenter study of patients with ejection fractions of 35% or less, we compared baseline plasma norepinephrine, plasma renin activity, plasma atrial natriuretic factor, and plasma arginine vasopressin in 56 control subjects, 151 patients with left ventricular dysfunction (no overt heart failure), and 81 patients with overt heart failure before randomization. Median values for plasma norepinephrine (p = 0.0001), plasma atrial natriuretic factor (p less than 0.0001), plasma arginine vasopressin (p = 0.006), and plasma renin activity (p = 0.03) were significantly higher in patients with left ventricular dysfunction than in normal control subjects. Neuroendocrine values were highest in patients with overt heart failure. Plasma renin activity was normal in patients with left ventricular dysfunction without heart failure who were not receiving diuretics and was significantly increased (p less than 0.05) in patients on diuretic therapy. We conclude that neuroendocrine activation occurs in patients with left ventricular dysfunction and no heart failure. Neuroendocrine activation is further increased as overt heart failure ensues and diuretics are added to therapy.

Arginine Vasopressin↗
PubMed1990

Routine medical management of acute myocardial infarction. Lessons from overviews of recent randomized controlled trials.

In recent years, several large randomized trials have clarified the role of various interventions in acute myocardial infarction. There is clear evidence that thrombolytic therapy, aspirin, and beta-blockers reduce mortality. Both aspirin and beta-blockers also reduce reinfarction and stroke. Of the thrombolytic agents, comparative trials have established that tissue plasminogen activator and streptokinase have similar effects on mortality, morbidity, and left ventricular function. There appears to be an increased risk of cerebral hemorrhage with tissue plasminogen activator. The benefits of heparin in conjunction with aspirin and a thrombolytic agent are unclear and, at best, are likely to be modest. Heparin increases the risk of hemorrhagic complications twofold. Although trials of vasodilators conducted before the widespread use of thrombolytic therapy and aspirin have been promising, newer trials are needed to evaluate their effects among patients receiving these agents. The aggregate of all trials of the routine use of calcium antagonists or antiarrhythmic agents indicates that these agents do not improve survival.

Adrenergic beta-Antagonists↗
PubMed1990

Effect of acute angiotensin converting enzyme inhibition on left ventricular filling in patients with congestive heart failure. Relation to right ventricular volumes.

To examine the manner in which changes in diastolic performance can contribute to the effect of vasodilation in patients with left ventricular (LV) systolic dysfunction, we examined the effect of acute inhibition of angiotensin converting enzyme with intravenous enalaprilat on early LV diastolic filling. We studied 43 patients with congestive heart failure and depressed LV systolic function (mean ejection fraction +/- SD, 0.24 +/- 0.06), performing radionuclide ventriculography before and after administration of 1.25 mg intravenous enalaprilat. We measured the effect of enalaprilat on the maximum rate of early LV diastolic filling normalized in four different ways and related these changes to both LV and right ventricular (RV) volumes. Enalaprilat induced a small but statistically significant reduction in LV end-systolic volume and increase in LV ejection fraction. For the entire patient group, there was no significant change in LV peak filling rate after enalaprilat administration. For individual patients, however, the effect of enalaprilat on peak filling rate was related to resting RV end-diastolic and end-systolic volumes. In patients with enlarged RV end-diastolic volumes (greater than or equal to 120 ml/m2), mean peak filling rate increased from 1.38 +/- 0.6 to 1.71 +/- 0.6 end-diastolic volumes (EDV)/sec and from 244 +/- 131 to 297 +/- 162 ml/sec/m2 after enalaprilat administration, whereas no change in mean peak filling rate was observed in patients with nondilated RVs. These observations were present regardless of the method of normalizing peak filling rate. Thus, the response of LV peak filling rate to enalaprilat is influenced by the presence of RV dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Calcium channel blockers in acute myocardial infarction and unstable angina: an overview.

OBJECTIVE: To assess the effects of calcium channel blockers on development of infarcts, reinfarction, and mortality. DESIGN: A systematic overview of all randomised trials of calcium channel blockers in myocardial infarction and unstable angina. PATIENTS: 19,000 Patients in 28 randomised trials. RESULTS: In the trials of myocardial infarction 873 deaths occurred among 8870 patients randomised to active treatment compared with 825 deaths among 8889 control patients (odds ratio of 1.06, 95% confidence interval of 0.96 to 1.18). There was no evidence of a beneficial effect on development and size of infarcts or rate of reinfarction. The results were similar in short term trials in which treatment was confined to the acute phase and those in which treatment was started some weeks later and continued for a year or two. There was no evidence of heterogeneity among different calcium channel blockers in their effects on any end point. The results were similar in the unstable angina trials (110 out of 561 patients treated with calcium channel blocker compared with 104 out of 548 controls developed a myocardial infarction; 14 out of 591 treated compared with nine out of 578 controls died). CONCLUSIONS: Calcium channel blockers do not reduce the risk of initial or recurrent infarction or death when given routinely to patients with acute myocardial infarction or unstable angina.

Acute Disease↗
PubMed1989

Influence of beta blockade on exercise capacity and heart rate response after human orthotopic and heterotopic cardiac transplantation.

It has been reported that use of beta blockers may not be safe after cardiac transplantation because the denervated hearts may be largely dependent on circulating catecholamines to increase cardiac output. Therefore, the effects of intravenous propranolol were studied during maximal treadmill exercise in 7 patients with heterotopic and 6 with orthotopic cardiac transplantations. An average decrease of about 15% in exercise duration (p less than 0.001), a 34% reduction in systolic blood pressure increase (p less than 0.05) and a 40% attenuation in heart rate increase (p less than 0.001) were observed after beta blockade. In patients with heterotopic transplantation, beta blockade produced similar effects on heart rate in the denervated donor hearts and the innervated recipient hearts during and after mild exercise. During peak exercise, beta blockade attenuated the rate to a greater extent in the donor hearts. Although the denervated donor heart is more sensitive to beta blockade than the innervated recipient heart during exercise, no adverse effects were observed. Beta-blocker therapy should be considered for cardiac transplant patients if longer-term studies confirm their safe use in these patients.

Adrenergic beta-Antagonists↗
PubMed1989

Early intravenous beta-blockade in acute myocardial infarction.

The clinical effects of early intravenous beta-blockade followed by short-term oral treatment in acute myocardial infarction (MI) have been studied in 30 randomized trials totaling almost 28,000 patients. This treatment reduces the incidence of infarction by 10-15% in patients with threatened MI, reduces infarct size by 20-30%; reduces the incidence of nonfatal reinfarction, nonfatal cardiac arrest and mortality each by about 15%. Treatment has to start within 12 h of the onset of symptoms to be able to reduce measures of infarct size and infarct development. If patients are carefully selected serious side effects are rare and reversible. Based on the different presumed mechanisms of benefit it would be reasonable to expect the combination of i.v. beta-blockade and other therapies of proven benefit to be more beneficial than either class of agent used alone.

Adrenergic beta-Antagonists↗
PubMed1989

Relation of baseline characteristics to suppression of ventricular arrhythmias during placebo and active antiarrhythmic therapy in patients after myocardial infarction.

In the Cardiac Arrhythmia Pilot Study (CAPS), patients early (6-60 days) after acute myocardial infarction (MI) with ventricular premature complexes (VPCs) of over 10 per hour were randomized to receive, unaware, therapy with one of four antiarrhythmic drugs (n = 402) or placebo (n = 100). Treatment success was defined as 70% or more decrease in VPC rate and 90% or more decrease in VPC runs. If the first active drug was ineffective, a second drug was given. If placebo was ineffective, a second placebo was given. To determine whether or not baseline clinical characteristics predict the response to antiarrhythmic therapy, 10 baseline variables were selected for investigation: age, prior MI, time from CAPS MI to randomization, ejection fraction, baseline VPC frequency, presence of runs (greater than or equal to 3 consecutive VPCs, greater than or equal to 100 beats/min), beta-blocker therapy, digitalis therapy, MI transmurality, and MI location. At the end of the first drug treatment, apparent treatment success in patients receiving placebo was associated on univariate analysis with absence of prior MI, with trends for younger age and Q wave MI, whereas in patients receiving active therapies, higher ejection fraction and younger age were associated with better suppression. In the encainide and flecainide treatments, where the greatest response was observed, absence of prior MI, higher ejection fraction, and younger age were associated with more successful treatment. In a multivariate analysis with these variables, ejection fraction and age remained significant for all active therapies, absence of prior MI and ejection fraction remained significant in the encainide and flecainide treatments, and absence of prior MI in the placebo treatment. Few variables except ejection fraction were associated with VPC suppression during the 1-year follow-up, and only lower ejection fraction and older age related to loss of long-term suppression. Thus, there are only a few independent baseline clinical variables (notably, ejection fraction) that substantially affect antiarrhythmic drug efficacy in suppressing VPCs in patients early after MI. Some variables, however, may be associated with spontaneous arrhythmia variability, leading to an apparent (placebo) response. These findings will be helpful in designing and interpreting treatment studies in patients after MI.

Anilides↗
PubMed1989

An overview of randomized trials of rehabilitation with exercise after myocardial infarction.

Of 22 randomized trials of rehabilitation with exercise after myocardial infarction (MI), one trial had results that achieved conventional statistical significance. To determine whether or not these studies, in the aggregate, show a significant benefit of rehabilitation after myocardial infarction, we performed an overview of all randomized trials, involving 4,554 patients; we evaluated total and cardiovascular mortality, sudden death, and fatal and nonfatal reinfarction. For each endpoint, we calculated an odds ratio (OR) and 95% confidence interval (95% CI) for the trials combined. After an average of 3 years of follow-up, the ORs were significantly lower in the rehabilitation than in the comparison group: specifically, total mortality (OR = 0.80 [0.66, 0.96]), cardiovascular mortality (OR = 0.78 [0.63, 0.96]), and fatal reinfarction (OR = 0.75 [0.59, 0.95]). The OR for sudden death was significantly lower in the rehabilitation than in the comparison group at 1 year (OR = 0.63 [0.41, 0.97]). The data were compatible with a benefit at 2 (OR = 0.76 [0.54, 1.06]) and 3 years (OR = 0.92 [0.69, 1.23]), but these findings were not statistically significant. For nonfatal reinfarction, there were no significant differences between the two groups after 1 (OR = 1.09 [0.76, 1.57]), 2 (OR = 1.10 [0.82, 1.47]), or 3 years (OR = 1.09 [0.88, 1.34]) of follow-up. The observed 20% reduction in overall mortality reflects a decreased risk of cardiovascular mortality and fatal reinfarction throughout at least 3 years and a reduction in sudden death during the 1st year after infarction and possibly for 2-3 years. With respect to the independent effects of the physical exercise component of cardiac rehabilitation, the relatively small number of "exercise only" trials, combined with the possibility that they may have had a formal or informal nonexercise component precludes the possibility of reaching any definitive conclusion. To do so would require a randomized trial of sufficient size to distinguish between no effect and the most plausible effect based on the results of this overview.

Clinical Trials as Topic↗
PubMed1989

Changes in hypertension treatment and in congestive heart failure mortality in the United States.

The use of antihypertensive agents has increased in recent years and has been more marked among individuals in older age groups (65-74 years) than in middle-aged groups (45-54 years). Because hypertension is a strong risk factor for the development of congestive heart failure, more common use of antihypertensive agents would be expected to reduce the incidence of congestive heart failure. Examination of the national death statistics reveals decreases in congestive heart failure mortality at younger ages with mortality increases at older ages. The reasons for these divergent trends in congestive heart failure mortality in different ages and the apparent inconsistency with respect to the changes in the use of antihypertensive drugs are explored. We speculate that antihypertensive treatment does not completely prevent congestive heart failure but merely postpones its development by several decades.

Adult↗
PubMed1988

Effects of prophylactic lidocaine in suspected acute myocardial infarction. An overview of results from the randomized, controlled trials.

The effects of prophylactic lidocaine hydrochloride on early ventricular fibrillation and death in patients with suspected acute myocardial infarction were investigated in an overview of 14 randomized trials. During follow-up intervals of one to four hours in the trials of intramuscular lidocaine infusion (6961 patients) and 24 to 48 hours in the trials of intravenous lidocaine injection (2194 patients), a total of 103 cases of ventricular fibrillation and 137 deaths were recorded. Overall, allocation to lidocaine was associated with a reduction in the odds of ventricular fibrillation of about one third, with a 95% confidence interval that ranged from a 3% to a 56% reduction. There was no evidence of any beneficial effect on early mortality; indeed, the odds of early death were about one third greater among patients allocated lidocaine, though this difference was not statistically significant (95% confidence interval, 2% reduction to 95% increase). Because of the small numbers of reported events, the short follow-up periods, and the unavailability of data for some specific causes of death, even an overview of all the trial results does not provide good evidence as to whether prophylactic lidocaine is likely to be helpful or harmful. To answer this question reliably, future trials will need to involve large numbers of patients and prolonged follow-up.

Clinical Trials as Topic↗